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Posttranscriptional regulation of TSC-22 (TGF-beta-stimulated clone-22) gene by TGF-beta 1.

TSC-22 gene was composed of three exons and its length was approximately 5.5 kb including 2.9 kb promoter region. The transcription starting site was located at 7 and 29 bp downstream from TATA box. Promoter analysis revealed that 2146 bp of TSC-22 promoter was activated by several differentiation inducing drugs. Although originally TSC-22 was isolated as a TGF-beta-inducible gene, TSC-22 promoter was not activated by the enhanced TGF-beta signaling. We found 3 copies of the Shaw-Kamens sequence (AUUUA) in the human TSC-22 mRNA 3'-UTR and identified three proteins (40, 20, and 15 kDa) which bound to this. Only the 40 kDa protein-RNA complex was decreased by treatment with TGF-beta 1. Moreover, the TSC-22 mRNA 3'-UTR destabilized the heterologous luciferase mRNA, but the destabilization was recovered with TGF-beta 1. These observations suggest that up-regulation of TSC-22 mRNA by TGF-beta 1 is achieved by mRNA stabilization, but not by transcriptional activation.[1]

References

  1. Posttranscriptional regulation of TSC-22 (TGF-beta-stimulated clone-22) gene by TGF-beta 1. Uchida, D., Omotehara, F., Nakashiro, K., Tateishi, Y., Hino, S., Begum, N.M., Fujimori, T., Kawamata, H. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
 
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